Spinal cord modulation for inhibiting pain via short pulse width waveforms, and associated systems and methods

ABSTRACT

Short pulse width spinal cord modulation for inhibiting pain with reduced side effects and associated systems and methods are disclosed. In particular embodiments, modulation signal has pulse widths in the range of from about 10 microseconds to about 50 microseconds may be applied to the patient&#39;s spinal cord region to address chronic pain without using paresthesia or tingling to mask or cover the patient&#39;s sensation of pain. In other embodiments, modulation in accordance with similar parameters can be applied to other spinal or peripheral locations to address other indications.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a divisional of U.S. patent application Ser.No. 14/534,769, filed on Nov. 6, 2014, which claims priority to U.S.Provisional Application No. 61/901,255, filed on Nov. 7, 2013incorporated herein by reference.

TECHNICAL FIELD

The present disclosure is directed generally to spinal cord modulationfor inhibiting pain via short pulse width waveforms, and associatedsystems and methods.

BACKGROUND

Neurological stimulators have been developed to treat pain, movementdisorders, functional disorders, spasticity, cancer, cardiac disorders,and various other medical conditions. Implantable neurologicalstimulation systems generally have an implantable pulse generator andone or more leads that deliver electrical pulses to neurological tissuevia electrodes. For example, neurological stimulation systems for spinalcord stimulation (SCS) may include cylindrical leads that include a leadbody with a circular cross-sectional shape and one or more conductiverings spaced apart from each other at the distal end of the lead body.The conductive rings operate as individual electrodes and, in manycases, the SCS leads are implanted percutaneously through a large needleinserted into the epidural space, with or without the assistance of astylet.

Once implanted, the pulse generator applies electrical pulses to theneurological tissue via the electrodes, which in turn modifies thefunction of the patient's nervous system. Conventional SCS paintreatments, for example, apply low-frequency (e.g., less than 1,500 Hz),large pulse width (e.g., greater than 50 microsecond) electrical pulsesto the spinal cord to generate sensations of tingling or paresthesiathat mask or otherwise alter the patient's sensation of pain. In somecases, patients report that the generated sensations of tingling orparesthesia are perceived as more pleasant and/or less uncomfortablethan the underlying pain sensation. Studies have suggested (at leastanecdotally) that longer pulse width electrical pulses (e.g., in excessof 450 microseconds) achieve better pain-paresthesia overlap and comfortfor patients (Lee et al., Predicted effects of pulse width programmingin spinal cord stimulation: a mathematical modeling study, Med Biol EngComput (2011) 49:765-774).

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a partially schematic illustration of an implantable spinalcord modulation system positioned at the spine to deliver therapeuticsignals in accordance with several embodiments of the presentdisclosure.

FIG. 1B is a partially schematic, cross-sectional illustration of apatient's spine, illustrating representative locations for implantedlead bodies in accordance with embodiments of the disclosure.

FIGS. 2A and 2B are flow diagrams illustrating methods conducted inaccordance with embodiments of the disclosure.

FIG. 2C is a schematic illustration of a representative waveform havingfeatures in accordance with embodiments of the present technology.

FIG. 3 illustrates an arrangement of leads.

FIG. 4 is a partially schematic illustration of a lead body configuredin accordance with an embodiment of the disclosure.

FIGS. 5A-5C are partially schematic illustrations of extendible leadsconfigured in accordance with several embodiments of the disclosure.

FIGS. 6A-6C are partially schematic illustrations of multifilar leadsconfigured in accordance with several embodiments of the disclosure.

DETAILED DESCRIPTION 1.0 Introduction

The present technology is directed generally to spinal cord modulationand associated systems and methods for inhibiting pain via waveformswith short pulse widths (e.g., less than 50 microseconds). In at leastsome embodiments, the waveforms also have frequencies (and/or frequencyelements or components, e.g., fundamental frequencies) in the range offrom about 2 Hz to about 1,500 Hz. In general, the short pulse widthcharacteristics of the signal, alone or in combination with other signalparameters (e.g., frequency and/or amplitude) can produce pain reliefwithout using the generation of paresthesia to mask the patient'ssensation of pain. Several embodiments also provide simplified spinalcord modulation systems and components, and simplified procedures forthe practitioner and/or the patient. Specific details of certainembodiments of the disclosure are described below with reference tomethods for modulating one or more target neural populations (e.g.,nerves) or sites of a patient, and associated implantable structures forproviding the modulation. Although selected embodiments are describedbelow with reference to modulating the dorsal column, dorsal horn,dorsal root, dorsal root entry zone, and/or other particular regions ofthe spinal column to control pain, the modulation may in some instancesbe directed to other neurological structures and/or target neuralpopulations of the spinal cord and/or other neurological tissues. Someembodiments can have configurations, components or procedures differentthan those described in this section, and other embodiments mayeliminate particular components or procedures. A person of ordinaryskill in the relevant art, therefore, will understand that thedisclosure may include other embodiments with additional elements,and/or may include other embodiments without several of the featuresshown and described below with reference to FIGS. 1A-6C.

In general terms, aspects of many of the following embodiments aredirected to producing a therapeutic effect that includes pain reductionin the patient. The therapeutic effect can be produced by inhibiting,suppressing, down-regulating, preventing, or otherwise modulating theactivity of the affected neural population. In many embodiments of thepresently disclosed techniques, therapy-induced paresthesia is not aprerequisite to achieving pain reduction.

FIG. 1A schematically illustrates a representative treatment system 100for providing relief from chronic pain and/or other conditions, arrangedrelative to the general anatomy of a patient's spinal cord 191. Thesystem 100 can include an implantable pulse generator 101, which may beimplanted subcutaneously within a patient 190 and may be coupled to asignal delivery element 110. In a representative example, the signaldelivery element 110 includes a lead or lead body 111 that carriesfeatures for delivering therapy to the patient 190 after implantation.The pulse generator 101 can be connected directly to the lead 111, or itcan be coupled to the lead 111 via a communication link 102 (e.g., anextension). Accordingly, the lead 111 can include a terminal sectionthat is releasably connected to an extension at a break 114 (shownschematically in FIG. 1A). This allows a single type of terminal sectionto be used with patients of different body types (e.g., differentheights). As used herein, the terms lead and lead body include any of anumber of suitable substrates and/or support members that carry devicesfor providing therapy signals to the patient 190. For example, the lead111 can include one or more electrodes or electrical contacts thatdirect electrical signals into the patient's tissue, such as to providefor patient relief. In other embodiments, the signal delivery element110 can include devices other than a lead body (e.g., a paddle, aleadless implantable electrode, etc.) that also direct electricalsignals and/or other types of signals to the patient 190.

The pulse generator 101 can transmit signals (e.g., electrical signals)to the signal delivery element 110 that up-regulate (e.g., stimulate orexcite) and/or down-regulate (e.g., inhibit or suppress) target nerves.As used herein, and unless otherwise noted, the terms “modulate” and“modulation” refer generally to signals that have either type of theforegoing effects on the target nerves. The pulse generator 101 caninclude a machine-readable (e.g., computer-readable) medium containinginstructions for generating and transmitting suitable therapy signals inaccordance with the methods and/or parameters described herein. Thepulse generator 101 and/or other elements of the system 100 can includeone or more processors 107, memories 108 and/or input/output devices.Accordingly, the process of providing modulation signals and/orexecuting other associated functions can be performed bycomputer-executable instructions contained on computer-readable media,e.g., at the processor(s) 107 and/or memory(s) 108. The pulse generator101 can include multiple portions, elements, and/or subsystems (e.g.,for directing signals in accordance with multiple signal deliveryparameters), housed in a single housing, as shown in FIG. 1A, or inmultiple housings.

The pulse generator 101 can also receive and respond to an input signalreceived from one or more sources. The input signals can direct orinfluence the manner in which the therapy instructions are selected,executed, updated and/or otherwise performed. The input signal can bereceived from one or more sensors 112 (one is shown schematically inFIG. 1 for purposes of illustration) that are carried by the pulsegenerator 101 and/or distributed outside the pulse generator 101 (e.g.,at other patient locations) while still communicating with the pulsegenerator 101. The sensors 112 can provide inputs that depend on orreflect patient state (e.g., patient position, patient posture and/orpatient activity level), and/or inputs that are patient-independent(e.g., time). In other embodiments, inputs can be provided by thepatient and/or the practitioner, as described in further detail later.

In some embodiments, the pulse generator 101 can obtain power togenerate the therapy signals from an external power source 103. Theexternal power source 103 can transmit power to the implanted pulsegenerator 101 using electromagnetic induction (e.g., RF signals). Forexample, the external power source 103 can include an external coil 104that communicates with a corresponding internal coil (not shown) withinthe implantable pulse generator 101. The external power source 103 canbe portable for ease of use.

In another embodiment, the pulse generator 101 can obtain the power togenerate therapy signals from an internal power source, in addition toor in lieu of the external power source 103. For example, the implantedpulse generator 101 can include a non-rechargeable battery or arechargeable battery to provide such power. When the internal powersource includes a rechargeable battery, the external power source 103can be used to recharge the battery. The external power source 103 canin turn be recharged from a suitable power source (e.g., conventionalwall power).

In some cases, a trial modulator 105 can be coupled to the signaldelivery element 110 during an initial implant procedure, prior toimplanting the pulse generator 101. For example, a practitioner (e.g., aphysician and/or a company representative) can use the trial modulator105 to vary the modulation parameters provided to the signal deliveryelement 110 in real time, and select optimal or particularly efficaciousparameters. These parameters can include the position of the signaldelivery element 110, as well as the characteristics of the electricalsignals provided to the signal delivery element 110. In a typicalprocess, the practitioner uses a cable assembly 120 to temporarilyconnect the trial modulator 105 to the signal delivery device 110. Thecable assembly 120 can accordingly include a first connector 121 that isreleasably connected to the trial modulator 105, and a second connector122 that is releasably connected to the signal delivery element 110.Accordingly, the signal delivery element 110 can include a connectionelement that allows it to be connected to a signal generator eitherdirectly (if it is long enough) or indirectly (if it is not). Thepractitioner can test the efficacy of the signal delivery element 110 inan initial position. The practitioner can then disconnect the cableassembly 120, reposition the signal delivery element 110, and reapplythe electrical modulation. This process can be performed iterativelyuntil the practitioner obtains the desired position for the signaldelivery device 110. Optionally, the practitioner may move the partiallyimplanted signal delivery element 110 without disconnecting the cableassembly 120.

After the position of the signal delivery element 110 and appropriatesignal delivery parameters are established using the trial modulator105, the patient 190 can receive therapy via signals generated by thetrial modulator 105, generally for a limited period of time. In arepresentative application, the patient 190 receives such therapy forone week. During this time, the patient wears the cable assembly 120 andthe trial modulator 105 outside the body. Assuming the trial therapy iseffective or shows the promise of being effective, the practitioner thenreplaces the trial modulator 105 with the implanted pulse generator 101,and programs the pulse generator 101 with parameters selected based onthe experience gained during the trial period. Optionally, thepractitioner can also replace the signal delivery element 110. Once theimplantable pulse generator 101 has been positioned within the patient190, the signal delivery parameters provided by the pulse generator 101can still be updated remotely via a wireless external programmer 109(e.g., a physician's remote, laptop, PDA, tablet, etc.) and/or awireless patient programmer 106 (e.g., a patient remote). Generally, thepatient 190 has control over fewer parameters than does thepractitioner. For example, the capability of the patient programmer 106may be limited to only starting and/or stopping the pulse generator 101,and/or adjusting the signal amplitude.

In any of the foregoing embodiments, the parameters in accordance withwhich the pulse generator 101 provides signals can be adjusted duringportions of the therapy regimen. For example, the frequency, amplitude,pulse width and/or signal delivery location can be adjusted inaccordance with a preset program, patient and/or physician inputs,and/or in a random or pseudorandom manner. Such parameter variations canbe used to address a number of potential clinical situations, includingchanges in the patient's perception of pain, changes in the preferredtarget neural population, and/or patient accommodation or habituation.

2.0 Representative Therapy Parameters

FIG. 1B is a cross-sectional illustration of the spinal cord 191 and anadjacent vertebra 195 (based generally on information from Crossman andNeary, “Neuroanatomy,” 1995 (published by Churchill Livingstone)), alongwith the locations at which leads 110 can be implanted in representativepatients. The spinal cord 191 is situated between a ventrally locatedventral body 196 and the dorsally located transverse process 198 andspinous process 197. Arrows V and D identify the ventral and dorsaldirections, respectively. The spinal cord 191 itself is located withinthe dura mater 199, which also surrounds portions of the nerves exitingthe spinal cord 191, including the dorsal roots 193, dorsal root entryzone 188, and dorsal root ganglia 194. The leads 110 (indicated by leads110 b) can be positioned just off the spinal cord midline 189 (e.g.,about 1 mm. offset) in opposing lateral directions so that the two leads110 b are spaced apart from each other by about 2 mm, in particularembodiments. In other embodiments, a single lead 110 a can be positionedat the midline 189. In still further embodiments, lead(s) can bepositioned at or proximate to the dorsal root 193 (as shown by lead 110c) and/or at or proximate to the dorsal root ganglia 194 (as shown bylead 110 d).

FIGS. 2A and 2B are flow diagrams illustrating methods for treatingpatients in accordance with particular embodiments of the presentdisclosure. Manufacturers or other suitable entities can provideinstructions to practitioners for executing these and other methodsdisclosed herein. Manufacturers can also program devices of thedisclosed systems to carry out at least some of these methods. FIG. 2Aillustrates a method 600 that includes implanting a signal generator ina patient (block 610). The signal generator can be implanted at thepatient's lower back or other suitable location. The method 600 furtherincludes implanting a signal delivery device (e.g., a lead, paddle orother suitable device) at the patient's spinal cord region (block 620).This portion of the method can in turn include implanting the device(e.g., active contacts of the device) at a vertebral level ranging fromabout T8 to about T12 (e.g., about T8-T12, inclusive) (block 621), andat a lateral location ranging from the spinal cord midline to the DREZ,inclusive (block 622). At block 630, the method includes applying ashort pulse width waveform, via the signal generator and the signaldelivery device. In particular examples, the signal (or at least aportion of the signal) can have pulses with pulse widths ranging fromabout 10-50 microseconds, or from about 20-40 microseconds, or fromabout 25-35 microseconds, or from about 30-35 microseconds, or about 30microseconds. The amplitude of the waveform (e.g., the amplitudes of theindividual pulses) can be from about 0.5-20 mA, or from about 2-18 mA,or from about 5-15 mA, or from about 7-10 mA, or about 0.5-7 mA. Thefrequency of the signal (or at least a portion of the signal) can be ator below 1.5 kHz, e.g., from about 2 Hz to about 1.5 kHz, or from about500 Hz to about 1.5 kHz, or from about 700 Hz to about 1.5 kHz, or fromabout 1 kHz to about 1.5 kHz, or about 1.2 kHz, or from about 500 Hz toabout 1.2 kHz. In one representative example, the waveform includes afrequency of 1,200 Hz, a pulse width of 30 microseconds, and anamplitude that provides pain relief without generating paresthesia(generally between 0.5-20 mA).

The method 600 further includes suppressing, inhibiting or otherwisereducing the patient's pain, e.g., chronic low back pain (block 640).This portion of the method can in turn include reducing pain withoutunwanted sensory effects and/or limitations (block 641), and/or withoutmotor effects (block 642). For example, block 641 can include reducingor eliminating pain without reducing patient perception of othersensations, and/or without triggering additional pain and/orparesthesia. Block 642 can include reducing or eliminating pain withouttriggering muscle action and/or without interfering with motor signaltransmission.

FIG. 2B illustrates a method 601 that includes features in addition tothose described above with reference to FIG. 2A. For example, theprocess of applying a short pulse width waveform (block 630) can includedoing so over a wide amplitude range (e.g., over any of the amplituderanges described immediately above) without creating unwanted sideeffects, such as undesirable sensations and/or motor interference (block631). In another embodiment, the process of applying a short pulse widthwaveform can include applying the waveform at a fixed amplitude (block632).

The process of inhibiting, suppressing or otherwise reducing patientpain (block 640) can include doing so without creating paresthesia(block 643), or in association with a deliberately generated paresthesia(block 644). For example, paresthesia may be used by the practitionerfor site selection (e.g., to determine the location at which activeelectrodes are positioned). In addition to the above, reducing patientpain can include doing so with relative insensitivity to patientattributes that standard SCS is normally highly sensitive to (block645). These attributes can include patient movement (block 646) and/orpatient position (block 647).

FIG. 2C illustrates a representative waveform 650 having pulses 660 andother characteristics, parameters and/or features in accordance withrepresentative embodiments of the present technology. The pulses 660 caninclude cathodic phase pulses 651 paired with anodic phase pulses 652.The cathodic phase pulses 651 can be separated from the anodic phasepulses 652 by an interphase interval 653. A pulse pair interval 656 canseparate one pulse pair (e.g., a cathodic phase pulse 651 paired with ananodic phase pulse 652) from the next. The frequency of the waveform 650is generally defined as the inverse of the period 657. The period 657 isin turn the sum of a cathodic phase pulse width 654, an anodic phasepulse width 655, the interphase interval 653 and the pulse pair interval656.

The values described above with reference to FIG. 2A for pulse width canapply to the cathodic phase pulse width 654 and/or the anodic phasepulse width 655. The cathodic and anodic phase pulse widths 654, 655 areequal in some embodiments, and unequal in others. In general, the areaenclosed by the cathodic phase pulses 651 and the anodic phase pulses652, as shown in FIG. 2C, can be equal. Accordingly, the overall chargeapplied to the patient as a result of the cathodic phase pulses 651 canbe equal and opposite to the overall charge applied to the patient as aresult of the anodic phase pulses 652. This charge balancing approachcan reduce or eliminate potential adverse effects associated with chargeaccumulation within the patient.

In general, e.g., when the cathodic and anodic pulse widths 654, 655 areequal, the amplitudes of the cathodic phase pulses 651 and the anodicphase pulses 652 are also equal, but in at least some embodiments, theamplitudes can be different. For example, when the pulse widths of thecathodic phase pulses 651 are different than those of the anodic phasepulses 652, the respective amplitudes of the pulses can also bedifferent, and can be selected to balance the overall charge applied tothe patient.

In particular embodiments, the interphase interval 653 can have a valueof from about 10 microseconds to about 980 milliseconds. The pulse pairinterval 656 can have a value in the range of from about 10 microsecondsto about 980 milliseconds. In at least some embodiments, the value ofpulse pair interval 656 results from the selection of the cathodic phasepulse width 654, the anodic phase pulse width 655, the interphaseinterval 653 and the period 657. In other embodiments, the pulse pairinterval 656 can be selected first with other parameters (e.g., theinterphase interval 653) being secondary. In still further embodiments,the parameters can be selected in other orders, with the pulse width(s)(anodic and/or cathodic) generally being an independent variable.

FIG. 3 is a schematic illustration of a typical lead placement usedduring a representative treatment regimen. Two leads 111 (shown as afirst lead 111 a and a second lead 111 b) can be positioned generallyend-to-end to provide a modulation capability that extends over severalvertebral levels of the patients' spine. The leads 111 a, 111 b can bepositioned to overlap slightly, to account for possible shifts in leadlocation. During the course of the therapy, contacts C of the two leads111 a, 111 b can be activated on one lead at a time. In other words, thecontacts C of only one lead 111 can be active at any one time, andsignals need not directed between the contacts C located on differentleads 111. While two leads can be used is some cases, it is expectedthat in other cases, a single lead can be positioned at the appropriatevertebral level. The lead can have more widely spaced contacts toachieve the same or similar effects as those described herein as will bedescribed in greater detail below with reference to FIG. 4.

The contacts C of each lead 111 a, 111 b have a width W2 ofapproximately 3 mm, and are separated from each other by a distance D1of approximately 1 mm. Accordingly, the center-to-center spacing Sbetween neighboring contacts C is approximately 4 mm. The leads 111 a,111 b can be positioned at or close to the patients' spinal midline 189.In a representative embodiment one lead can be positioned on one side ofthe midline 189, and the other lead can be positioned on the other sideof the patients' midline 189. The leads 111 a, 111 b can be positionedat any of a variety of locations within a relatively wide window W1having an overall width of ±3-5 mm from the midline 189 (e.g., anoverall width of 6-10 mm), without significantly affecting the efficacyof the treatment.

In one embodiment, one or more of the above-described waveformparameters and lead placements are used to produce an incompleteconduction block (e.g., an incomplete block of afferent and/or efferentsignal transmission) at the dorsal root level. This block may occur atthe dorsal column, dorsal horn, and/or dorsal root entry zone, inaddition to or in lieu of the dorsal root. In any of these cases, theconduction block is selective to and/or preferentially affects thesmaller AO and/or C fibers and is expected to produce a decrease inexcitatory inputs to the second order neurons, thus producing a decreasein pain signals supplied along the spinal thalamic tract.

In another embodiment, one or more of the above-described waveformparameters and lead placements are used to activate an interneuron pooland thus increase the inhibition of inputs into second order neurons.This activation can, in effect, desensitize the second order neurons andconvert them closer to a normal state before the effects of the chronicpain associated signals have an effect on the patient.

In still another embodiment, one or more of the above-described waveformparameters and lead placements are used to reduce the hypersensitivityof neurons by restoring or moving the “baseline” of the neural cells inchronic pain patients toward the normal baseline and firing frequency ofnon-chronic pain patients. This effect can in turn reduce the sensationof pain in this patient population without affecting other neuraltransmissions (for example, touch, heat, etc.).

In another embodiment, one or more of the above-described waveformparameters and lead placements are used to (1) reduce neuraltransmissions entering the spinal cord at the dorsal root and/or thedorsal root entry zone, and/or (2) reduce neural activity at the dorsalhorn itself. It is generally known that chronic pain patients may be ina state of prolonged sensory sensitization at both the nociceptiveafferent neurons (e.g., a peripheral nerve and its associated dorsalroot) and at higher order neural systems (e.g., the dorsal horn neuron).It is also known that the dorsal horn neurons (e.g., the width dynamicrange or WDR cells) are sensitized in chronic pain states. Chronic paincan be associated with an acute “windup” of the WDR cells (e.g., to ahyperactive state). It is believed that the therapy signals appliedusing the disclosed parameters may be used to reduce pain by reducing,suppressing, and/or attenuating the afferent nociceptive inputsdelivered to the WDR cells, as it is expected that these inputs, unlessattenuated, can be responsible for the sensitized state of the WDRcells. In one embodiment, the disclosed parameters may be used to actdirectly on the WDR cells to desensitize these cells. The effect of thepresently disclosed therapy on peripheral inputs may produce short termpain relief, and the effect on the WDR cells may produce longer termpain relief.

In one embodiment, one or more of the above-described waveformparameters and lead placements are used to modulate glial cells in thenervous system. Glial cells were traditionally thought to play primarilya structural role in the nervous system, for example by surroundingneurons, holding neurons in place, providing electrical insulation, anddestroying pathogens. However, in recent years it has been suggestedthat glial cells play a role in the transmission of chronic pain byreleasing various mediators such as nitric oxide, pro-inflammatorycytokines, excitatory amino acids, and prostaglandins. Release of thesemediators can cause the release of substance P and excitatory aminoacids by peripheral nerves, which in turn results in action potentialgeneration. Substance P and excitatory amino acid release can alsofurther activate glial cells, creating a positive feedback loop. Glialcells communicate via slow inward calcium currents, which are activatedby a variety of factors including potassium. The short pulse widthwaveform parameters disclosed herein may be used to reduce extracellularpotassium levels by primary afferent inhibition, thereby reducing glialcell activity. The short pulse width waveform parameters disclosedherein may also be used to produce pain reduction in part by changingthe conductance of fast sodium channels in neurons and/or glial cells,thereby specifically down-regulating those sodium channels that are mostinvolved with chronic pain.

As disclosed herein, short pulse width electrical modulation can be usedto normalize pathological neural networks associated with fast sodiumchannel activity and/or expression by attenuating pathology-inducedsodium channel activity and modulating glial neuronal cell interaction(GNI). Based on this, the present application provides methods anddevices for attenuating pathology-induced sodium channel activity,modulating GNI, and treating various conditions associated with fastsodium channel activity and/or expression and GNI.

In certain embodiments, methods are provided for attenuatingpathology-induced sodium channel activity by applying short pulse widthelectrical stimulation to a target tissue or organ (e.g., the spinalcord). This attenuation may result in decreased activity and/orexpression of one or more fast sodium channels, including for exampleNaV1.8 or NaV1.9. In certain embodiments, decreased activity and/orexpression of one or more fast sodium channels results in decreasedglial cell and/or neuronal activity. In certain embodiments, attenuationof pathology-induced sodium channel activity may also result inincreased activity and/or expression of one or more slow sodiumchannels, including for example NaV1.3.

4.0 Expected Benefits Associated With Certain Embodiments

As discussed above, an expected benefit of short pulse width waveforms(e.g., having pulse widths within the ranges described above) is thatwhen applied at the appropriate amplitude, to the appropriate neuralpopulation, such pulses can effectively reduce or eliminate patient painwithout the signal producing, creating, or generating paresthesia. Inaddition to providing pain relief without paresthesia, such waveformscan produce pain relief with less power than is required for waveformshaving longer pulse widths, depending upon the values selected for othersignal delivery parameters.

In any of the foregoing embodiments, aspects of the therapy provided tothe patient may be varied within or outside the parameters describedabove, while still obtaining beneficial results for patients sufferingfrom chronic pain (e.g., chronic lower back pain, chronic leg pain,chronic limb pain, etc.). For example, the location of the lead body(and in particular, the lead body electrodes or contacts) can be variedover the significant lateral and/or axial ranges described above. Othercharacteristics of the applied signal can also be varied. For example,the frequency of the signal (or at least a portion of the signal) can beat or below 1.5 kHz, e.g., from about 2 Hz to about 1.5 kHz, or fromabout 500 Hz to about 1.5 kHz, or from about 700 Hz to about 1.5 kHz, orfrom about 1 kHz to about 1.5 kHz, or about 1.2 kHz, or from about 500Hz to about 1.2 kHz. The amplitude of the signal can range from about0.1 mA to about 20 mA in a particular embodiment, and in furtherparticular embodiments, can range from about 0.5 mA to about 10 mA, orabout 0.5 mA to about 7 mA, or about 0.5 mA to about 5 mA. The amplitudeof the applied signal can be ramped up and/or down. In particularembodiments, the amplitude can be increased or set at an initial levelto establish a therapeutic effect, and then reduced to a lower level tosave power without forsaking efficacy. In particular embodiments, thesignal amplitude refers to the electrical current level, e.g., forcurrent-controlled systems. In other embodiments, the signal amplitudecan refer to the electrical voltage level, e.g., for voltage-controlledsystems. In particular embodiments, the signal (or at least a portion ofthe signal) can have pulses with pulse widths ranging from about 10-50microseconds, or from about 20-40 microseconds, or from about 25-35microseconds, or from about 30-35 microseconds, or about 30microseconds. The specific values selected for the foregoing parametersmay vary from patient to patient and/or from indication to indicationand/or on the basis of the selected vertebral location. In addition, themethodology may make use of other parameters, in addition to or in lieuof those described above, to monitor and/or control patient therapy. Forexample, in cases for which the pulse generator includes a constantvoltage arrangement rather than a constant current arrangement, thecurrent values described above may be replaced with correspondingvoltage values. In another example, it is expected that the signal canhave short pulse widths over a wide range of frequencies while producingpain relief without paresthesia. For example, pulse widths of 10-50microseconds may be used to produce such results at frequencies rangingfrom about 2 Hz to about 1,500 Hz.

Patients can receive multiple signals in accordance with still furtherembodiments of the disclosure. For example, patients can receive two ormore signals, each with different signal delivery parameters. In oneparticular example, the signals are interleaved with each other. Inother embodiments, patients can receive sequential “packets” or “bursts”of pulses at different frequencies, with each packet having a durationof less than one second, several seconds, several minutes, or longerdepending upon the particular patient and indication.

In still further embodiments, the duty cycle can be from about 50%-100%.In further embodiments, the duty cycle can have a value of less than50%, e.g., at or less than 20% or at or less than 10%. In yet anotherembodiment, the duty cycle parameters can be set to 2 seconds on, 20seconds off. In still further embodiments, the duty cycle parameters canbe set to 20 seconds on, 120 seconds off.

5.0 Representative Lead Configurations

FIG. 4 is a partially schematic illustration of a lead 910 having firstand second contacts C1, C2 positioned to deliver modulation signals inaccordance with particular embodiments of the disclosure. The contactsare accordingly positioned to contact the patient's tissue whenimplanted. The lead 910 can include at least two first contacts C1 andat least two second contacts C2 to support bipolar modulation signalsvia each contact grouping. In one aspect of this embodiment, the lead910 can be elongated along a major or lead axis A, with the contacts C1,C2 spaced equally from the major axis A. In general, the term elongatedrefers to a lead or other signal delivery element having a length (e.g.,along the spinal cord) greater than its width. The lead 910 can have anoverall length L (over which active contacts are positioned) that islonger than that of typical leads. In particular, the length L can besufficient to position first contacts C1 at one or more vertebrallocations (including associated neural populations), and position thesecond contacts C2 at another vertebral location (including associatedneural populations) that is spaced apart from the first and that issuperior the first. For example, the first contacts C1 may be positionedat vertebral levels T8-T12 to treat low back pain, and the secondcontacts C2 may be positioned at superior vertebral locations (e.g.,cervical locations) to treat arm pain. Representative lead lengths arefrom about 30 cm to about 150 cm, and in particular embodiments, fromabout 40 cm to about 50 cm. Pulses may be applied to both groups ofcontacts in accordance with several different arrangements. For examplepulses provided to one group may be interleaved with pulses applied tothe other, or the same signal may be rapidly switched from one group tothe other. In other embodiments, the signals applied to individualcontacts, pairs of contacts, and/or contacts in different groups may bemultiplexed in other manners. In any of these embodiments, each of thecontacts C1, C2 can have an appropriately selected surface area, e.g.,in the range of from about 3 mm² to about 25 mm², and in particularembodiments, from about 8 mm² to about 15 mm². Individual contacts on agiven lead can have different surface area values, within the foregoingranges, than neighboring or other contacts of the lead, with valuesselected depending upon features including the vertebral location of theindividual contact.

Another aspect of an embodiment of the lead 910 shown in FIG. 4 is thatthe first contacts C1 can be spaced apart (e.g., closest edge to closestedge) by a first distance S1 that is greater than a corresponding seconddistance S2 between immediately neighboring second contacts C2. In arepresentative embodiment, the first distance S1 can range from about 3mm up to a distance that corresponds to one-half of a vertebral body,one vertebral body, or two vertebral bodies (e.g., about 16 mm, 32 mm,or 64 mm, respectively). In another particular embodiment, the firstdistance S1 can be from about 5 mm to about 15 mm. This increasedspacing can reduce the complexity of the lead 910, and can still provideeffective treatment to the patient. In still further embodiments, theinferior first contacts C1 can have the close spacing S2, and thesuperior second contacts C2 can have the wide spacing S1, depending uponpatient indications and/or preferences. In still further embodiments, asnoted above, contacts at both the inferior and superior locations canhave the wide spacing. In other embodiments, the lead 910 can includeother arrangements of different contact spacings, depending upon theparticular patient and indication. For example, the widths of the secondcontacts C2 (and/or the first contacts C1) can be a greater fraction ofthe spacing between neighboring contacts than is representedschematically in FIG. 4. The distance S1 between neighboring firstcontacts C1 can be less than an entire vertebral body (e.g., 5 mm or 16mm) or greater than one vertebral body while still achieving benefitsassociated with increased spacing, e.g., reduced complexity. The lead910 can have all contacts spaced equally (e.g., by up to about twovertebral bodies), or the contacts can have different spacings, asdescribed above. Two or more first contacts C1 can apply modulation atone vertebral level (e.g., T9) while two or more additional firstcontacts C1 can provide modulation at the same or a different frequencyat a different vertebral level (e.g., T10).

In some cases, it may be desirable to adjust the distance between theinferior contacts C1 and the superior contacts C2. For example, the lead910 can have a coil arrangement (like a telephone cord) or otherlength-adjusting feature that allows the practitioner to selectivelyvary the distance between the sets of contacts. In a particular aspectof this arrangement, the coiled portion of the lead can be locatedbetween the first contacts C1 and the second contacts C2. For example,in an embodiment shown in FIG. 5A, the lead 910 can include a proximalportion 910 a carrying the first contacts C1, a distal portion 910 ccarrying the second contacts C2, and an intermediate portion 910 bhaving a pre-shaped, variable-length strain relief feature, for example,a sinusoidally-shaped or a helically-shaped feature. The lead 910 alsoincludes a stylet channel or lumen 915 extending through the lead 910from the proximal portion 910 a to the distal portion 910 c.

Referring next to FIG. 5B, the practitioner inserts a stylet 916 intothe stylet lumen 915, which straightens the lead 910 for implantation.The practitioner then inserts the lead 910 into the patient, via thestylet 916, until the distal portion 910 c and the associated secondcontacts C2 are at the desired location. The practitioner then securesthe distal portion 910 c relative to the patient with a distal leaddevice 917 c. The distal lead device 917 c can include any of a varietyof suitable remotely deployable structures for securing the lead,including, but not limited to an expandable balloon.

Referring next to FIG. 5C, the practitioner can partially or completelyremove the stylet 916 and allow the properties of the lead 910 (e.g.,the natural tendency of the intermediate portion 910 b to assume itsinitial shape) to draw the proximal portion 910 a toward the distalportion 910 c. When the proximal portion 910 a has the desired spacingrelative to the distal portion 910 c, the practitioner can secure theproximal portion 910 a relative to the patient with a proximal leaddevice 917 a (e.g., a suture or other lead anchor). In this manner, thepractitioner can select an appropriate spacing between the firstcontacts C1 at the proximal portion 910 a and the second contacts C2 atdistal portion 910 c that provides effective treatment at multiplepatient locations along the spine.

FIG. 6A is an enlarged view of the proximal portion 910 a of the lead910, illustrating an internal arrangement in accordance with aparticular embodiment of the disclosure. FIG. 6B is a cross-sectionalview of the lead 910 taken substantially along line 11B-11B of FIG. 6A.Referring now to FIG. 6B, the lead 910 can include multiple conductors921 arranged within an outer insulation element 918, for example, aplastic sleeve. In a particular embodiment, the conductors 921 caninclude a central conductor 921 a. In another embodiment, the centralconductor 921 a can be eliminated and replaced with the stylet lumen 915described above. In any of these embodiments, each individual conductor921 can include multiple conductor strands 919 (e.g., a multifilararrangement) surrounded by an individual conductor insulation element920. During manufacture, selected portions of the outer insulation 918and the individual conductor insulation elements 920 can be removed,thus exposing individual conductors 921 at selected positions along thelength of the lead 910. These exposed portions can themselves functionas contacts, and accordingly can provide modulation to the patient. Inanother embodiment, ring (or cylinder) contacts are attached to theexposed portions, e.g., by crimping or welding. The manufacturer cancustomize the lead 910 by spacing the removed sections of the outerinsulation element 918 and the conductor insulation elements 920 in aparticular manner. For example, the manufacturer can use a stencil orother arrangement to guide the removal process, which can include, butis not limited to, an ablative process. This arrangement allows the sameoverall configuration of the lead 910 to be used for a variety ofapplications and patients without major changes. In another aspect ofthis embodiment, each of the conductors 921 can extend parallel to theothers along the major axis of the lead 910 within the outer insulation918, as opposed to a braided or coiled arrangement. In addition, each ofthe conductor strands 919 of an individual conductor element 920 canextend parallel to its neighbors, also without spiraling. It is expectedthat these features, alone or in combination, will increase theflexibility of the overall lead 910, allowing it to be inserted with agreater level of versatility and/or into a greater variety of patientanatomies then conventional leads.

FIG. 6C is a partially schematic, enlarged illustration of the proximalportion 910 a shown in FIG. 6A. One expected advantage of the multifilarcable described above with reference to FIG. 6B is that the impedance ofeach of the conductors 921 can be reduced when compared to conventionalcoil conductors. As a result, the diameter of the conductors 921 can bereduced and the overall diameter of the lead 910 can also be reduced.One result of advantageously reducing the lead diameter is that thecontacts C1 may have a greater length in order to provide the requiredsurface area needed for effective modulation. If the contacts C1 areformed from exposed portions of the conductors 921, this is not expectedto present an issue. If the contacts C1 are ring or cylindricalcontacts, then in particular embodiments, the length of the contact maybecome so great that it inhibits the practitioner's ability to readilymaneuver the lead 910 during patient insertion. One approach toaddressing this potential issue is to divide a particular contact C1into multiple sub-contacts, shown in FIG. 6C as six sub-contacts C1 a-C1f. In this embodiment, each of the individual sub-contacts C1 a-C1 f canbe connected to the same conductor 921 shown in FIG. 6B. Accordingly,the group of sub-contacts connected to a given conductor 921 can operateessentially as one long contact, without inhibiting the flexibility ofthe lead 910.

As noted above, one feature of the foregoing arrangements is that theycan be easy to design and manufacture. For example, the manufacturer canuse different stencils to provide different contact spacings, dependingupon specific patient applications. In addition to or in lieu of theforegoing effect, the foregoing arrangement can provide for greatermaneuverability and facilitate the implantation process by eliminatingring electrodes and/or other rigid contacts, or dividing the contactsinto subcontacts. In other embodiments, other arrangements can be usedto provide contact flexibility. For example, the contacts can be formedfrom a conductive silicone, e.g., silicone impregnated with a suitableloading of conductive material, such as platinum, iridium or anothernoble metal.

Yet another feature of an embodiment of the lead shown in FIG. 4 is thata patient can receive effective therapy with just a single bipolar pairof active contacts. If more than one pair of contacts is active, eachpair of contacts can receive the identical waveform, so that activecontacts can be shorted to each other. In another embodiment, theimplanted pulse generator (not visible in FIG. 4) can serve as a returnelectrode. For example, the pulse generator can include a housing thatserves as the return electrode, or the pulse generator can otherwisecarry a return electrode that has a fixed position relative to the pulsegenerator. Accordingly, the modulation provided by the active contactscan be unipolar modulation, as opposed to the more typical bipolarstimulation associated with standard SCS treatments.

6.0 Representative Modulation Locations and Indications

Many of the embodiments described above were described in the context oftreating chronic, neuropathic low back pain with modulation signalsapplied to the lower thoracic vertebrae (T8-T12). In other embodiments,modulation signals having parameters (e.g., frequency, pulse width,amplitude, and/or duty cycle) generally similar to those described abovecan be applied to other patient locations to address other indications.For example, while the foregoing methodologies included applyingmodulation at lateral locations ranging from the spinal cord midline tothe DREZ, in other embodiments, the modulation may be applied to theforamen region, laterally outward from the DREZ. In other embodiments,the modulation may be applied to other spinal levels of the patient. Forexample, modulation may be applied to the sacral region and moreparticularly, the “horse tail” region at which the sacral nerves enterthe sacrum. Urinary incontinence and fecal incontinence representexample indications that are expected to be treatable with modulationapplied at this location. In other embodiments, the modulation may beapplied to other thoracic vertebrae. For example, modulation may beapplied to thoracic vertebrae above T8. In a particular embodiment,modulation may be applied to the T3-T6 region to treat angina.Modulation can be applied to high thoracic vertebrae to treat painassociated with shingles. Modulation may be applied to the cervicalvertebrae to address chronic regional pain syndrome and/or total bodypain, and may be used to replace neck surgery. Suitable cervicallocations include vertebral levels C3-C7, inclusive. In otherembodiments, modulation may be applied to the occipital nerves, forexample, to address migraine headaches.

As described above, modulation in accordance with the foregoingparameters may also be applied to treat acute and/or chronic nociceptivepain. For example, modulation in accordance with these parameters can beused during surgery to supplement and/or replace anesthetics (e.g., aspinal tap). Such applications may be used for tumor removal, kneesurgery, and/or other surgical techniques. Similar techniques may beused with an implanted device to address post-operative pain, and canavoid the need for topical lidocaine. In still further embodiments,modulation in accordance with the foregoing parameters can be used toaddress other peripheral nerves. For example, modulation can be applieddirectly to peripheral nerves to address phantom limb pain.

From the foregoing, it will be appreciated that specific embodiments ofthe disclosure have been described herein for purposes of illustration,but that various modifications may be made without deviating from thedisclosure. For example, the specific parameter ranges and indicationsdescribed above may be different in further embodiments. The leaddescribed above with reference to FIGS. 4-6C can have more than twogroups of contacts, and/or can have other contact spacings in otherembodiments. In some embodiments, as described above, the signalamplitude applied to the patient can be constant. In other embodiments,the amplitude can vary in a preselected manner, e.g., via rampingup/down, and/or cycling among multiple amplitudes. The signal deliveryelements can have an epidural location, as discussed above with regardto FIG. 1B, and in other embodiments, can have an extradural location.In particular embodiments described above, signals having the foregoingcharacteristics are expected to provide therapeutic benefits forpatients having low back pain and/or leg pain, when stimulation isapplied at vertebral levels from about T8 to about T12. In at least someother embodiments, it is believed that this range can extend from aboutT5 to about L1.

Certain aspects of the disclosure described in the context of particularembodiments may be combined or eliminated in other embodiments. Forexample, therapies directed to particular indications may be combined inparticular embodiments. Further, while advantages associated withcertain embodiments have been described in the context of thoseembodiments, other embodiments may also exhibit such advantages, and notall embodiments need necessarily exhibit such advantages to fall withinthe scope of the present disclosure. Accordingly, the present disclosureand associated technology can encompass other embodiments not expresslyshown or described herein.

I claim:
 1. A spinal cord stimulation system for reducing or eliminatingpain in a patient, the system comprising: an implantable signalgenerator having a computer-readable medium with instructions togenerate and transmit a non-paresthesia-producing therapy signal,wherein at least a portion of the therapy signal is at a frequency offrom 1,000 Hz to 1,500 Hz, with a pulse width in a pulse width rangefrom 10 microseconds to 50 microseconds, and a current amplitude in acurrent amplitude range from 0.5 to 20 mA; and a signal delivery deviceelectrically coupleable to the implantable signal generator and designedto be implanted in the patient's epidural space to deliver the therapysignal to the dorsal column of the patient's spinal cord.
 2. The systemof claim 1, wherein the implantable signal generator generates thetherapy signal at a duty cycle.
 3. The system of claim 2, wherein theduty cycle is 50-100%.
 4. The system of claim 2, wherein the frequencyis applied throughout the length of an on period in the duty cycle. 5.The system of claim 2, wherein the frequency is applied during a portionof an on period in the duty cycle.
 6. The system of claim 1, wherein thefrequency is from 500 Hz to 1,200 Hz.
 7. The system of claim 1, whereinthe frequency is from 1,200 Hz to 1,500 Hz.
 8. The system of claim 1,wherein the amplitude is from 2 to 18 mA.
 9. The system of claim 1,wherein the amplitude is from 5 to 15 mA.
 10. The system of claim 1,wherein the amplitude is from 7 to 10 mA.
 11. The system of claim 1,wherein the amplitude is from 0.5 to 7 mA.
 12. The system of claim 1,wherein the therapy signal is delivered at a current amplitude of about2.5 mA.
 13. The system of claim 1, wherein the pulsewidth is from 20 to40 microseconds.
 14. The system of claim 1, wherein the pulsewidth isfrom 25 to 35 microseconds.
 15. The system of claim 1, wherein thepulsewidth is from 30 to 35 microseconds.
 16. The system of claim 1,wherein at least a portion of the therapy signal is a square-wavesignal.
 17. The system of claim 1, wherein the signal delivery device isa percutaneous lead.
 18. The system of claim 1, wherein the signaldelivery device is a paddle lead.
 19. A spinal cord stimulation systemfor reducing or eliminating pain in a patient, the system comprising: animplantable signal generator that, in operation, generates anon-paresthesia-producing therapy signal, wherein at least a portion ofthe therapy signal is at a frequency of from 1,000 Hz to 1,500 Hz, witha pulse width in a pulse width range from 10 microseconds to 50microseconds, and a current amplitude in a current amplitude range from0.5 mA to 20 mA; and a signal delivery device electrically coupled tothe implantable signal generator to deliver the therapy signal to thedorsal column of the patient's spinal cord.
 20. The system of claim 19,wherein the implantable signal generator generates the therapy signal ata duty cycle.
 21. The system of claim 20, wherein the duty cycle is100%.
 22. The system of claim 20, wherein the duty cycle is 50-100%. 23.The system of claim 20, wherein the frequency is applied throughout thelength of an on period in the duty cycle.
 24. The system of claim 20,wherein the frequency is applied during a portion of an on period in theduty cycle.
 25. The system of claim 19, wherein the therapy signal isdelivered at a current amplitude of 2.5 mA.
 26. The system of claim 19,wherein at least a portion of the therapy signal is a square-wavesignal.
 27. The system of claim 19, wherein the signal delivery deviceis a percutaneous lead.
 28. The system of claim 19, wherein the signaldelivery device is a paddle lead.
 29. The system of claim 19, whereinthe signal delivery device is an elongated lead having one or moreelectrodes.
 30. The system of claim 19, wherein the signal deliverydevice is an elongated lead having a bipole arrangement of electrodes.31. The system of claim 19, wherein the frequency is from 500 Hz to1,200 Hz.